485 results match your criteria Advances In Protein Chemistry[Journal]

Regulation of Rho guanine nucleotide exchange factors by G proteins.

Adv Protein Chem 2007 ;74:189-228

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Monomeric Rho GTPases regulate cellular dynamics through remodeling of the cytoskeleton, modulation of immediate signaling pathways, and longer-term regulation of gene transcription. One family of guanine nucleotide exchange factors for Rho proteins (RhoGEFs) provides a direct pathway for regulation of RhoA by cell surface receptors coupled to heterotrimeric G proteins. Some of these RhoGEFs also contain RGS domains that can attenuate signaling by the G(12) and G(13) proteins. Read More

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Kinetic analysis of G protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells.

Adv Protein Chem 2007 ;74:167-88

Institute of Pharmacology and Toxicology, University of Würzburg, D-97078 Würzburg, Germany.

We describe and review methods for the kinetic analysis of G protein-coupled receptor (GPCR) activation and signaling that are based on optical methods. In particular, we describe the use of fluorescence resonance energy transfer (FRET) as a means of analyzing conformational changes within a single protein (for example a receptor) or between subunits of a protein complex (such as a G protein heterotrimer) and finally between distinct proteins (such as a receptor and a G protein). These methods allow the analysis of signaling kinetics in intact cells with proteins that retain their essential functional properties. Read More

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Activation of G protein-coupled receptors.

Adv Protein Chem 2007 ;74:137-66

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.

G protein-coupled receptors (GPCRs) mediate responses to hormones and neurotransmitters, as well as the senses of sight, smell, and taste. These remarkably versatile signaling molecules respond to structurally diverse ligands. Many GPCRs couple to multiple G protein subtypes, and several have been shown to activate G protein-independent signaling pathways. Read More

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Some mechanistic insights into GPCR activation from detergent-solubilized ternary complexes on beads.

Adv Protein Chem 2007 ;74:95-135

Department of Pathology and Cancer Center, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131, USA.

The binding of full and partial agonist ligands (L) to G protein-coupled receptors (GPCRs) initiates the formation of ternary complexes with G proteins [ligand-receptor-G protein (LRG) complexes]. Cyclic ternary complex models are required to account for the thermodynamically plausible complexes. It has recently become possible to assemble solubilized formyl peptide receptor (FPR) and beta(2)-adrenergic receptor (beta(2)AR) ternary complexes for flow cytometric bead-based assays. Read More

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How do receptors activate G proteins?

Adv Protein Chem 2007 ;74:67-93

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

Heterotrimeric G proteins couple the activation of heptahelical receptors at the cell surface to the intracellular signaling cascades that mediate the physiological responses to extracellular stimuli. G proteins are molecular switches that are activated by receptor-catalyzed GTP for GDP exchange on the G protein alpha subunit, which is the rate-limiting step in the activation of all downstream signaling. Despite the important biological role of the receptor-G protein interaction, relatively little is known about the structure of the complex and how it leads to nucleotide exchange. Read More

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Structural basis of effector regulation and signal termination in heterotrimeric Galpha proteins.

Adv Protein Chem 2007 ;74:1-65

Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

This chapter addresses, from a molecular structural perspective gained from examination of x-ray crystallographic and biochemical data, the mechanisms by which GTP-bound Galpha subunits of heterotrimeric G proteins recognize and regulate effectors. The mechanism of GTP hydrolysis by Galpha and rate acceleration by GAPs are also considered. The effector recognition site in all Galpha homologues is formed almost entirely of the residues extending from the C-terminal half of alpha2 (Switch II) together with the alpha3 helix and its junction with the beta5 strand. Read More

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Structural models of amyloid-like fibrils.

Adv Protein Chem 2006 ;73:235-82

Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, California 90095, USA.

Amyloid fibrils are elongated, insoluble protein aggregates deposited in vivo in amyloid diseases, and amyloid-like fibrils are formed in vitro from soluble proteins. Both of these groups of fibrils, despite differences in the sequence and native structure of their component proteins, share common properties, including their core structure. Multiple models have been proposed for the common core structure, but in most cases, atomic-level structural details have yet to be determined. Read More

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January 2007

From the polymorphism of amyloid fibrils to their assembly mechanism and cytotoxicity.

Adv Protein Chem 2006 ;73:217-33

M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, CH-4056, Basel, Switzerland.

Extracellular amyloid deposits are present in a variety of diseases. They contain amyloid fibrils that arise from the association of proteins or peptides. At the molecular level, all these fibrils share a common assembly principle based on a conformational change of the protein precursor leading to the formation of a cross-beta sheet structure. Read More

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January 2007

X-Ray fiber and powder diffraction of PrP prion peptides.

Adv Protein Chem 2006 ;73:181-215

Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA.

A conformational change from the alpha-helical, cellular form of prion to the beta-sheet, scrapie (infectious) form is the central event for prion replication. The folding mechanism underlying this conformational change has not yet been deciphered. Here, we review prion pathology and summarize X-ray fiber and powder diffraction studies on the N-terminal fragments of prion protein and on short sequences that initiate the beta-assembly for various fibrils, including poly(L-alanine) and poly(L-glutamine). Read More

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January 2007

Structure, function, and amyloidogenesis of fungal prions: filament polymorphism and prion variants.

Adv Protein Chem 2006 ;73:125-80

Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Infectious proteins (prions) became an important medical issue when they were identified as agents of the transmissible spongiform encephalopathies. More recently, prions have been found in fungi and their investigation has been facilitated by greater experimental tractability. In each case, the normal form of the prion protein may be converted into the infectious form (the prion itself) in an autocatalytic process; conversion may either occur spontaneously or by transmission from an already infected cell. Read More

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January 2007

Natural triple beta-stranded fibrous folds.

Adv Protein Chem 2006 ;73:97-124

Department of Materials Science and Technology, University of Crete, 710 03 Heraklion, Crete, Greece.

A distinctive family of beta-structured folds has recently been described for fibrous proteins from viruses. Virus fibers are usually involved in specific host-cell recognition. They are asymmetric homotrimeric proteins consisting of an N-terminal virus-binding tail, a central shaft or stalk domain, and a C-terminal globular receptor-binding domain. Read More

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January 2007

Beta-rolls, beta-helices, and other beta-solenoid proteins.

Adv Protein Chem 2006 ;73:55-96

Centre de Recherches de Biochimie Macromoléculaire, CNRS FRE-2593, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.

Beta-rolls and beta-helices belong to a larger group of topologically similar proteins with solenoid folds: because their regular secondary structure elements are exclusively beta-strands, they are referred to as beta-solenoids. The number of beta-solenoids whose structures are known is now large enough to support a systematic analysis. Here we survey the distinguishing structural features of beta-solenoids, also documenting their notable diversity. Read More

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January 2007

Beta-silks: enhancing and controlling aggregation.

Adv Protein Chem 2006 ;73:17-53

Zoology Department, Oxford University, OX1 3PS, United Kingdom.

It appears that fiber-forming proteins are not an exclusive group but that, with appropriate conditions, many proteins can potentially aggregate and form fibrils; though only certain proteins, for example, amyloids and silks, do so under normal physiological conditions. Even so, this suggests a ubiquitous aggregation mechanism in which the protein environment is at least as important as the sequence. An ideal model system in which forced and natural aggregation has been observed is silk. Read More

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January 2007

Beta-structures in fibrous proteins.

Adv Protein Chem 2006 ;73:1-15

Centre de Recherches de Biochimie Macromoléculaire, CNRS FRE-2593, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.

The beta-form of protein folding, one of the earliest protein structures to be defined, was originally observed in studies of silks. It was then seen in early studies of synthetic polypeptides and, of course, is now known to be present in a variety of guises as an essential component of globular protein structures. However, in the last decade or so it has become clear that the beta-conformation of chains is present not only in many of the amyloid structures associated with, for example, Alzheimer's Disease, but also in the prion structures associated with the spongiform encephalopathies. Read More

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January 2007

The importance of cooperative interactions and a solid-state paradigm to proteins: what Peptide chemists can learn from molecular crystals.

J J Dannenberg

Adv Protein Chem 2005 ;72:227-73

Department of Chemistry, City University of New York, Hunter College and the Graduate School New York, New York 10021.

Proteins and peptides in solution or in vivo share properties with both liquids and solids. More often than not, they are studied using the liquid paradigm rather than that of a solid. Studies of molecular crystals illustrate how the use of a solid paradigm may change the way that we consider these important molecules. Read More

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Thermodynamics Of alpha-Helix Formation.

Adv Protein Chem 2005 ;72:199-226

Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, Pennsylvania 17033.

The alpha-helix was the first proposed and experimentally confirmed secondary structure. The elegant simplicity of the alpha-helical structure, stabilized by hydrogen bonding between the backbone carbonyl oxygen and the peptide amide four residues away, has captivated the scientific community. In proteins, alpha-helices are also stabilized by the so-called capping interactions that occur at both the C- and the N-termini of the helix. Read More

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Peptide and protein folding and conformational equilibria: theoretical treatment of electrostatics and hydrogen bonding with implicit solvent models.

Adv Protein Chem 2005 ;72:173-98

Department of Molecular Biology and Center for Theoretical Biological Physics, The Scripps Research Institute, La Jolla, California 92037.

Since biomolecules exist in aqueous and membrane environments, the accurate modeling of solvation, and hydrogen bonding interactions in particular, is essential for the exploration of structure and function in theoretical and computational studies. In this chapter, we focus on alternatives to explicit solvent models and discuss recent advances in generalized Born (GB) implicit solvent theories. We present a brief review of the successes and shortcomings of the application of these theories to biomolecular problems that are strongly linked to backbone H-bonding and electrostatics. Read More

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How hydrogen bonds shape membrane protein structure.

Stephen H White

Adv Protein Chem 2005 ;72:157-72

Department of Physiology and Biophysics, University of California at Irvine, Irvine, California 92697.

The energetic cost of partitioning peptide bonds into membrane bilayers is prohibitive unless the peptide bonds participate in hydrogen bonds. However, even then there is a significant free energy penalty for dehydrating the peptide bonds that can only be overcome by favorable hydrophobic interactions. Membrane protein structure formation is thus dominated by hydrogen bonding interactions, which is the subject of this review. Read More

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Resonance Character of Hydrogen-bonding Interactions in Water and Other H-bonded Species.

F Weinhold

Adv Protein Chem 2005 ;72:121-55

Theoretical Chemistry Institute and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706.

Hydrogen bonding underlies the structure of water and all biochemical processes in aqueous medium. Analysis of modern ab initio wave functions in terms of natural bond orbitals (NBOs) strongly suggests the resonance-type "charge transfer" (CT) character of H-bonding, contrary to the widely held classical-electrostatic viewpoint that underlies current molecular dynamics (MD) modeling technology. Quantum cluster equilibrium (QCE) theory provides an alternative ab initio-based picture of liquid water that predicts proton-ordered two-coordinate H-bonding patterns, dramatically different from the ice-like picture of electrostatics-based MD simulations. Read More

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Hydrogen bonds in molecular mechanics force fields.

Jan Hermans

Adv Protein Chem 2005 ;72:105-19

Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.

This chapter reviews formulation and parametrization of molecular mechanics force fields with special attention to technical and inherent problems. Most striking among the shortcomings is the inadequacy of the simple point charge description as a means to describe energy and forces of interactions between polar molecules and between polar groups in macromolecules, including hydrogen bonds. The current state of efforts to improve the description of polar interactions is discussed. Read More

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Modeling Polarization in Proteins and Protein-ligand Complexes: Methods and Preliminary Results.

Adv Protein Chem 2005 ;72:79-104

Department of Chemistry, Columbia University, New York, New York 10025.

This chapter discusses methods for modeling electronic polarization in proteins and protein-ligand complexes. Two different approaches are considered: explicit incorporation of polarization into a molecular mechanics force field and the use of mixed quantum mechanics/molecular mechanics methods to model polarization in a restricted region of the protein or protein-ligand complex. A brief description is provided of the computational methodology and parameterization protocols and then results from two preliminary studies are presented. Read More

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Backbone-Backbone H-Bonds Make Context-Dependent Contributions to Protein Folding Kinetics and Thermodynamics: Lessons from Amide-to-Ester Mutations.

Adv Protein Chem 2005 ;72:39-78

Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, La Jolla, California 92037.

The contribution of backbone-backbone hydrogen bonds (H-bonds) to protein folding energetics has been controversial. This is due, at least in part, to the inability to perturb backbone-backbone H-bonds by traditional methods of protein mutagenesis. Recently, however, protein backbone mutagenesis has become possible with the development of chemical and biological methods to replace individual amides in the protein backbone with esters. Read More

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Potential functions for hydrogen bonds in protein structure prediction and design.

Adv Protein Chem 2005 ;72:1-38

Center for Studies in Physics and Biology, Rockefeller University, New York, New York 10021.

Hydrogen bonds are an important contributor to free energies of biological macromolecules and macromolecular complexes, and hence an accurate description of these interactions is important for progress in biomolecular modeling. A simple description of the hydrogen bond is based on an electrostatic dipole-dipole interaction involving hydrogen-donor and acceptor-acceptor base dipoles, but the physical nature of hydrogen bond formation is more complex. At the most fundamental level, hydrogen bonding is a quantum mechanical phenomenon with contributions from covalent effects, polarization, and charge transfer. Read More

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Structure and mechanism of DNA polymerases.

Adv Protein Chem 2005 ;71:401-40

Institute of Structural Molecular Biology, University College London and Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom.

DNA polymerases are molecular motors directing the synthesis of DNA from nucleotides. All polymerases have a common architectural framework consisting of three canonical subdomains termed the fingers, palm, and thumb subdomains. Kinetically, they cycle through various states corresponding to conformational transitions, which may or may not generate force. Read More

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December 2005

Cytoskeleton dynamics powers nematode sperm motility.

Adv Protein Chem 2005 ;71:383-99

MRC Laboratory of Molecular Biology, Hills Rd, Cambridge CB2 2QH, England.

Nematode sperm provide a simple and specialized system for studying the molecular mechanism of amoeboid cell motility. Locomotion is generated by the assembly dynamics of their cytoskeleton, which is based on the major sperm protein (MSP). Protrusive force is generated at the leading edge of the lamellipod by MSP filament formation and bundling, whereas the contractile force that drags the rearward cell body forward is generated by cytoskeleton disassembly. Read More

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December 2005

Rotary molecular motors.

Stephan Wilkens

Adv Protein Chem 2005 ;71:345-82

Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.

The F-, V-, and A-adenosine triphosphatases (ATPases) represent a family of evolutionarily related ion pumps found in every living cell. They either function to synthesize adenosine triphosphate (ATP) at the expense of an ion gradient or they act as primary ion pumps establishing transmembrane ion motive force at the expense of ATP hydrolysis. The A-, F-, and V-ATPases are rotary motor enzymes. Read More

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December 2005

The structure of microtubule motor proteins.

Adv Protein Chem 2005 ;71:299-344

Max-Planck-Unit for Structural Molecular Biology; Notkestrasse 85, 22607 Hamburg, Germany.

Microtubules are the intracellular tracks for two classes of motor proteins: kinesins and dyneins. During the past few years, the motor domain structures of several kinesins from different organisms have been determined by X-ray crystallography. Compared with kinesins, dyneins are much larger proteins and attempts to crystallize them have failed so far. Read More

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December 2005

Microtubules and maps.

Adv Protein Chem 2005 ;71:257-98

MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.

Microtubules are very dynamic polymers whose assembly and disassembly is determined by whether their heterodimeric tubulin subunits are in a straight or curved conformation. Curvature is introduced by bending at the interfaces between monomers. Assembly and disassembly are primarily controlled by the hydrolysis of guanosine triphosphate (GTP) in a site that is completed by the association of two heterodimers. Read More

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December 2005

X-ray diffraction studies of muscle and the crossbridge cycle.

Adv Protein Chem 2005 ;71:195-255

Biological Structure & Function Section, Biomedical Sciences Division, Imperial College Faculty of Medicine, London SW7 2AZ London, United Kingdom.

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December 2005